This research study is being conducted to examine the effects of daily inorganic nitrite treatment on the cardiometabolic and hormonal disturbances observed in overweight/obese adults with the metabolic syndrome and high blood pressure. Ultimately, oral nitrite therapy may have a major impact on the prevention and treatment of both diabetes and cardiovascular disease.

Cardiovascular disease remains the leading cause of death in the United States and worldwide. Several studies have demonstrated that fruit and vegetable rich diets significantly reduced blood pressure and reduced the risk of ischemic stroke and cardiovascular disease in general, the exact mechanisms remain poorly understood. Preclinical and clinical research over the last decade has revealed the important vasoprotective effects of nitrates and nitrites with regards to reduction in blood pressure, vascular inflammation and endothelial dysfunction. More recent findings suggest that inorganic nitrate and nitrite therapy may be involved in the regulation of glucose-insulin homeostasis.

For this reason, development of an oral formulation of nitrite salt represents a rational avenue of exploration for the treatment of cardiovascular diseases, whereby nitrite would ensure rapid acting effects upon absorption which can be further oxidized to nitrate via the enterosalivary circulation pathway. In this pathway, about 25% of circulating nitrate is concentrated in the saliva and reduced to nitrite by commensal mouth bacteria with nitrate reductase enzymes. The proposal is the first human study to investigate the inorganic nitrite effects (in any form) on insulin sensitivity in a patient population. This will be the second human trial using orally delivered nitrite (previously as aqueous solution).

Current use of ≥3 anti-hypertensive agents regardless of blood pressure control or normotensive on a single or double agent

Current use of PD5 inhibitors or organic nitrates

Not stable on treatments for the prior three months or not planning to remain on current dose of medications for blood pressure, contraception, etc.

Known chronic psychiatric or medical conditions including diabetes, liver or kidney disease or obesity syndromes

TSH >8 mIU/mL

Smoker

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01681810

Contacts

Contact: Kara S Hughan, MD

412-692-5173

Locations

United States, Pennsylvania

Montefiore Hospital of UPMC

Recruiting

Pittsburgh, Pennsylvania, United States, 15213

Principal Investigator: Kara S Hughan, MD

Sub-Investigator: Mark T Gladwin, MD

Sponsors and Collaborators

University of Pittsburgh

Investigators

Principal Investigator:

Kara S Hughan, MD

University of Pittsburgh

Study Director:

Mark Gladwin, MD

University of Pittsburgh

More Information

Responsible Party:

Kara Hughan, Assistant Professor of Pediatrics, University of Pittsburgh